Anti-angiogenic agents in metastatic colorectal cancer

Table 4 Bevacizumab plus chemotherapy as conversion therapy

Ref.	Regimen	Rate ofconversion (%)	Overallresponse (%)	Median PFS (mo)	Median OS (mo)
Bertolini et al[95]; Phase II	FOLFOX6 + bevacizumab	61.9	57.1	12.9	22.5
Wong et al[97]; Phase II	CAPE-OX + bevacizumab	40	78 (95%CI: 63-89)	NA1	NA1
Nasti et al[99]; Phase II	FOLFIRI + bevacizumab	N/A	66.7 (95%CI: 49.8-80.9)	14 (95%CI: 11-24)	38 (95%CI: 28 to NA)
Klinger et al[3]; Meta-analysis/phase II	CAPE-OX/FOLFOX + bevacizumab	N/A	38 vs 10 (P < 0.001)	NA2	67 (95%CI: 8.4-125.6)2
Gruenberger et al[96]; Phase II	CAPE-OX + bevacizumab	N/A	73.2	NA	NA
Gruenberger et al[102]; Phase II	FOLFOX/FOLFOXIRI + bevacizumab	49% (FOLFOX), 61% (FOLFOXIRI)	62% (95%CI: 45-77) (FOLFOX), 81% (95%CI: 65-91) (FOLFOXIRI)	11.5 (95%CI: 9.6-13.6) (FOLFOX), 18.6 (95%CI: 12.9-22.3) (FOLFOXIRI)	32.2 (FOLFOX), not yet reached (FOLFOXIRI)
Masi et al[100]; Phase II	FOLFOXIRI + bevacizumab	26	NA	NA	NA
Loupakis et al[34]; Phase III	FOLFOX/FOLFOXIRI + bevacizumab	53.1 (FOLFOX), 65.1 (FOLFOXIRI)	12 (FOLFOX), 15 (FOLFOXIRI)	NA	NA
Saltz et al[29]; Phase III	FOLFOX/Cape-OX + bevacizumab vs FOLFOX/Cape-OX + placebo	8.4 vs 6.1	38 vs 38	9.4 vs 8	21.3 vs 19.9
		P = NA	P = 0.99	P = 0.0023	P = 0.077
Loupakis et al[98]; meta-analysis	FOLFOXIR/Cape-IRI ± bevacizumab	NA	63 vs 28	NA3	NA
			P = 0.033
Osterlund et al[101]; retrospective analysis	FOLFIRI + bevacizumab	9	42%	8.8	18.4

¹Though median PFS and OS were not specifically reported by Wong et al[97], the 12-mo PFS was 50% (95%CI: 34%-64%) and 12-mo OS was 86% (95%CI: 70%-94%);

²The OS in this study was not reported as a single parameter given its sample population. Instead, it was reported as a function of tumor regression grade, or TRG. The median OS of 67 mo cited in this table was found in those patients with lower TRGs (histologically with more fibrosis/necrosis than tumor, or major histological response). This OS decreases to 44 mo (95%CI: 14.1-73.8) in those with higher TRGs (histologically with more tumor than fibrosis/necrosis, or no histological response). Though the median PFS was not reported in this study, the 5-year PFS was 34% in lower TRGs and 9% in higher TRGs;

³Again, the PFS was reported in this study as a function of TRGs. There was a PFS benefit in those with lower TRGs compared to those with higher TRGs such that for every 10 units in the percentage of necrosis, there was a 0.83 HR reduction (95%CI: 0.7-0.99, P = 0.04). NA: Not available; N/A: Not applicable; PFS: Progression-free survival; OS: Overall survival.